We propose to use our recent discovery that the forced expression of AID in hybridomas activates the somatic V region mutation to generate more effective monoclonal antibodies to agents used in bioterrorism. We will test high rates of V region mutation and isotype switching that can be activated in vivo with the conditional expression of AID. We will establish the optimum conditions for multiple rounds of mutation and selection to obtain the highest affinity antibodies with the full spectrum of isotypes. We will adapt techniques that we have used previously and we will develop new ones that will allow us to identify hybridoma subclones that are making human and mouse monoclonal antibodies that will more effectively neutralize the toxins and viruses and protect against microbial agents that are the primary agents used in bioterrorism and germ warfare. We will determine if such second-generation monoclonal antibodies to ricin and other toxins are truly more effective using mouse models.